Open Radical Cystectomy (ORC) is currently the gold standard treatment for muscle-invasive bladder cancer. While it is associated with adequate survival outcomes, it is also associated with considerable recovery time and postoperative morbidity. With the intent of making the surgery less invasive, the use of surgical robot has been applied in patients with bladder cancer. It has been hypothesized that Robotic-Assisted Radical Cystectomy (RARC) significantly improves time to functional recovery without compromising on the oncologic effectiveness. Phase 3 prospective randomized trials comparing the effectiveness of RARC to ORC are needed to validate this hypothesis. In keeping with NIH's mission to pursue research and apply knowledge that extends healthy life and reduces the burdens of illness and disability, we plan on conducting a phase 3 multi-institutional randomized comparative effectiveness clinical trial comparing oncologic and functional outcomes between RARC and ORC for bladder cancer patients. We will measure 2 year progression free survival, overall survival, patient reported and performance related measures of functional independence, perioperative morbidity and quality of life in each group. The value, interest and importance of conducting our proposed trial is validated by the active participation of 13 tertiary care academic centers located across the United States in our proposal. The participating clinical institutions are the University of Texas Health Science Center San Antonio, University of Chicago Medical Center, Vanderbilt University Medical Center, Stanford University Medical Center, University of California at Irvine Medical Center, Mayo Clinic in Scottsdale, Arizona, Henry Ford Health System, Detroit, University of Michigan Medical Center, Loyola University Medical Center, University of Minnesota Medical Center, Ohio State University Medical Center, University of Virginia Medical Center at Charlottesville and University of North Carolina Medical Center. The results from this study will be critical to determining the comparative effectiveness of RARC compared with ORC and potentially change the standard of care in the surgical approach for patients with bladder cancer. The exceedingly high volume of radical cystectomies performed at each of the participating institutions (more than 50 radical cystectomies per year at each institution) along with the wealth of experience accruing patients to NIH-funded randomized controlled trials (e.g. PCPT, MTOPS and SELECT) lends itself to significantly higher chances of patient accrual and willingness to participate. As we strive toward efficient utilization of healthcare resources, it is critical that we evaluate the true effectiveness of new technologies and determine whether the higher upfront costs are justified by improvements in other areas. There is a window of opportunity to gather randomized, prospective data, comparing RARC to ORC before the forces of the marketplace determine the standard of care.